| The amygdala plays a key role in emotional processing, and dysfunction of the amygdala is implicated in a variety of psychiatric disorders. Growing evidence suggests many disorders, including anxiety, depression, autism, and schizophrenia, are neurodevelopmental in origin. During development, brain circuits undergo "sensitive periods" when environmental factors have potent effects that include long-term consequences for emotional processing. We hypothesized that a risk factor for psychiatric disorders, prenatal stress, alters the trajectory of amygdala maturation and thereby influences emotional outcomes. In order to test this hypothesis, however, it was necessary to first understand how the amygdala typically develops. While a number of gross structural and functional changes have been identified in the normally developing amygdala, no studies have characterized amygdala development in terms of the function of neurons. Here, we report the first findings of changes to electrophysiology of the developing amygdala. We used patch clamp in ex vivo rat brain slices to describe the electrophysiology of amygdala neurons, discovering a number of changes. Amygdala neurons exhibited profound maturation of their intrinsic properties from birth through infancy, including reduced excitability, faster action potentials produced at higher rates, and altered expression of membrane currents and the ion channels that mediate them. Developing amygdala neurons also showed corresponding morphological changes, including expansion of dendritic arbors and the emergence of dendritic spines. In addition, synapses for the neurotransmitter gamma-aminobutyric acid (GABA) exhibited changes to kinetics, excitability, and synaptic plasticity. GABA regulates a variety of neurodevelopmental processes, including cell proliferation, migration, and differentiation, as well as synapse maturation, suggesting perturbation of the GABA system could alter amygdala development. We found that GABAergic function in the amygdala was altered by exposure to prenatal stress, with deficits emerging during infancy that preceded long-term changes to neuron excitability. Furthermore, these changes to amygdala maturation correspond with deficits in amygdala-dependent, emotional behavior. In sum, we have provided the first account of physiological development of amygdala neurons, and identified ways in which this process is perturbed by a risk factor for psychiatric illness. |
